We have recently developed techniques whereby acid secretion and buffer content of the stomach can be measured in humans. Using these methods we are studying gastric physiology and pathophysiology in humans in much the same way as has been previously possible only in animals with gastric pouches. During the past 28 months, during which time this grant has been in effect, we have concentrated on four major areas of research: 1) the effect of intragastric milieu on acid secretion and serum gastrin response to food (pH, amino acids and protein), 2) pathophysiology of duodenal ulcer (autoregulation of acid secretion and gastrin release and effect of enterogastrones), 3) methods of reducing food-stimulated acid secretion in duodenal ulcer patients (hormones, cholinergic blockade, and histamine H2-receptor blockade), and 4) therapy with H2-receptor antagonists. During the next 5 years our current and planned research includes: 1) study of the effect of gastric distention and specific dietary componenets on acid secretion and serum gastrin concentration in normal subjects and in patients with duodenal ulcer (gastric phase of acid secretion); 2) evaluation of the importance of serum gastrin concentration in regulating meal-stimulated acid secretion (in normal and duodenal ulcer subjects); 3) study the relative importance of cephalic, distention and chemical influences on acid secretion and serum gastrin concentration in response to a meal; 4) study of the effect of vagotomy on sham feeding response, serum gastrin response to a standard meal and the gastric response to an eaten steak meal in duodenal ulcer patients; and 5) comparison of buffer emptying in normal subjects and duodenal ulcer patients.